Proposed research is directed toward an understanding of the mechanisms of operation of two systems which contribute to hemostasis: The development of fibrin clot structure and the maintenance of platelet response and structural and metabolic integrity. (1) The development of fibrin clot structure involves, first, an enzymatic conversion by thrombin of fibrinogen into monomer fibrin. With fibrinogen in excess, monomer fibrin is stabilized by interaction and kept in solution. When stabilizing capacity is exceeded the dominant interactions between monomer fibrins leads to the formation of elongated protofibrils. Current results indicate that initial network is developed by nucleation of cooperative lateral interaction among protofibrils and that the differential release of A- and B-peptides is important in this respect. Nucleated lateral interaction then continues to develop the thicker fibrin fibrils characteristic of the mature network. Our objective is to specify reactions more quantitatively and to determine the particular effects on the reaction sequence produced by physiologically active agents. (2) Platelet metabolic activity and interactions with environmntal components control response to perturbation and the maintenance of structural and metabolic integrity. Fibrinogen appears mainly to be involved in the expression of ADP-induced aggregation response and plasma cofactor in the maintenance of integrity. Our objective is to complete analysis of results obtained on the relationship between ADP-induced aggregation response, platelet concentration and environmental refractive index as a means to more specific interpretation of the roles of plasma components.